The arterial partial pressure of CO2 (PaCO2) is intimately related to the acid base status of the blood. CO2 combines with water to form carbonic acid. The higher the PaCO2 the more acid is the blood. CO2 is formed in the body by metabolism and is eliminated from the lungs by ventilation. The relationship between PCO2 and ventilation is a rectangular hyperbola with PCO2 becoming infinite at low ventilations and reaching an asymptote of 0 at infinite ventilation. Ventilation is therefore controlled in response to chemosensitive neurons located in the brainstem and surrounding major arteries.
There are many occasions where it is required to induce a change in PaCO2 in a subject or patient. One example is to study the responses of various body systems to changes in CO2 such as the chemoreceptor cells themselves, breathing pattern, arousal, brain blood flow, coronary artery blood flow, ocular blood flow, renal blood flow, changes in blood vessel diameter in various organs and major arteries such as the brachial artery, and changes in brain waves, behavior and seizure threshold. We pick brain blood flow, blood volume and oxygen extraction fraction as an example for the use of changes in PaCO2. For example brain blood flow can be measured by various modalities that include trans-cranial Doppler, positron emission tomography (PET) and single proton emission tomography (SPECT), and nuclear magnetic resonance imaging (MRI) techniques such as blood oxygen level dependent (BOLD) and arterial spin labeling (ASL) echo. CO2 is used as the provocative stimulus to induce a change in blood flow and thus measure the vascular reactivity. Traditional methods have assumed that infusing CO2 into a mask will change the PaCO2. Infusing the CO2 into the mask changes the exhaled PCO2 but this is unreliably related to the PaCO2, the actual physiological stimulus at the site of action. It has been shown by Prisman et al1. and Hoskins et al.2 that this is totally ineffective (see discussion in Prisman1 and Mark et al.3,4). Still, infusion of CO2 into a mask or fixing the inspired PCO2 is nevertheless still used for studying brain vascular reactivity. With this method, one can detect a change in brain blood flow but because one doesn't know the PaCO2, the actual reactivity is unknown. For example, a small change in the measure of blood flow may be due to low reactivity or small change in PaCO2.
An improved method of implementing changes in PaCO2 has been presented by Prisman et al.1. The theory presented by Slessarev et al.5 is that sequential gas delivery provides good reliability in targeting a change in PaCO2. The theory of such targeting requires the delivery of a first gas which has a predetermined concentration of oxygen and CO2 to affect a PaCO2 at the first part of the breath and the remainder of the breath consists of a second gas which has CO2 concentration equal to the target PaCO2. Ito et al.6 applied such a circuit to spontaneously breathing humans and found that targeting with this system the expired partial pressure of CO2 was substantially equal to PaCO2 within about 2 mmHg. This is sufficiently accurate for most, but not all purposes. For example, calibration of MRI BOLD signals to measure oxygen consumption of the brain require as accurate determination of PaCO2 as can be obtained, and small discrepancies reduce the value of the calibration (Mark et al.). One source of error with the sequential gas delivery circuit is that some first gas continues to flow and be inhaled during the second gas delivery phase where it is desired that only second gas be inhaled. This is a limitation of all sequential gas delivery circuits. A variety of active or passive valves to prevent the first gas delivery during the phase where only second gas delivery is desired make the system more cumbersome, uncomfortable for the subject, and more expensive.